蛛网膜下腔出血（SAH）后发生白质损伤。我们的预实验结果提示：Netrin-1/KIF1A可能参与SAH后白质损伤。为此，我们提出假说：KIF1A介导Netrin-1分泌，SAH后二者表达下降；Netrin-1缺失导致其依赖型受体启动神经元凋亡和轴突脱髓鞘，促进白质损伤。为了验证该假说，我们拟利用大鼠SAH模型，应用western blot等检测SAH后白质中Netrin-1/KIF1A的水平；运用血肿产物处理神经元，筛选调控Netrin-1/KIF1A表达的关键血肿产物，并进行活体验证；应用基因调控和转基因，结合磁共振成像等技术，评估调控Netrin-1/KIF1A表达对白质损伤的影响；利用CO-IP等技术，阐述Netrin-1/KIF1A调控白质损伤的作用机制。本研究纵向从细胞、组织和活体三个层面，横向从分子生物学，神经影像和行为学三个层面开展研究，将为改善 SAH 预后提供新思路。

White matter injury after subarachnoid hemorrhage (SAH) is an important factor affecting the prognosis of SAH patients. Our preliminary experimental results showed that Netrin-1and KIF1A were probably involved in the pathological process of SAH-induced white matter injury. Thus, we propose the hypothesis: KIF1A mediates the secretion of Netrin-1. The expression of Netrin-1and KIF1A was decreased after SAH. In absent of Netrin-1, the dependent receptors of Netrin-1 promoted neuronal apoptosis and axonal demyelination, and finally white matter injury. To test the hypothesis, we firstly try to discover the effect of SAH on the expression of Netrin-1and KIF1A in the white matter of rats. Then, to choose the key clot component regulating the expression of Netrin-1and KIF1A, different clot components were separately used to treat cultured neurons. And the key clot component was injected into the brain to test its effects. Third, gene transfection, RNAi and transgenic mice are used to regulate the target gene expression, and then to evaluate the role of Netrin-1and KIF1A on SAH-induced white matter injury. And finally, by double immunofluorescence and co-immunoprecipitation, we demonstrate the mechanisms underlying the effect of Netrin-1and KIF1A on SAH-induced white matter injury. The longitudinal studies from three levels of cell, tissue and in vivo, horizontal researches from three levels of molecular biology, neuroimaging and molecular biology in this study will provide us new ideas and theoretical basis to improve the prognosis of SAH.